title: Regulation of gastrin, somatostatin and bombesin release from the isolated rat stomach by exogenous and endogenous gamma-aminobutyric acid.
abstract: OBJECTIVE
  gamma-Aminobutyric acid (GABA) is localized in epithelial cells and intrinsic nerve fibers of the gastric mucosa raising the possibility of a regulatory role for this transmitter. Therefore, it was the aim of the present study to examine the effect of exogenous and endogenous GABA on the neuroendocrine functions of the isolated perfused rat stomach.
  
  
  RESULTS
  Infusion of GABA (10(-8), 10(-6), 10(-4) M) caused a significant increase in gastrin release by 187 +/- 98, 328 +/- 43 and 493 +/- 84 pg/20 min and a significant decrease in somatostatin secretion by -540 +/- 203, -867 +/- 96 and -893 +/- 195 pg/20 min, respectively. Release of bombesin-like immunoreactivity (BLI) remained unchanged during infusion of GABA at the concentrations employed. The gastrin and somatostatin responses to 10(-4) M GABA were completely inhibited by the GABA(A) antagonist bicuculline (10(-5) M) and the cholinergic blocker atropine(l0(-7) M), whereas the GABAB antagonist CGP 35348 (5 x 10(-5) M) was ineffective. To evaluate the contribution of endogenous GABA in the vagal regulation of gastric neuroendocrine functions, gastrin, somatostatin and BLI responses to electrical stimulation of the vagal nerves were examined in the presence of bicuculline. Vagal stimulation (10 V, 10 Hz, 1 ms) induced a significant inhibition of somatostatin release by - 518 +/- 78 pg/10 min, which was attenuated to -259 +/- 143 pg/10 min (p < 0.05) in the presence of bicuculline. Atropine (10(-7) M) turned vagally induced inhibition of somatostatin release into a stimulation by 928 +/- 266 pg/10 min which was not altered by additionally infused bicuculline. Vagally stimulated gastrin release was reduced from 397 +/- 47 to 217 +/- 72 pg/10 min (p < 0.05) by bicuculline, while atropine had no effect. Vagally induced BLI release was not altered by bicuculline and atropine. Since the effect of bicuculline on vagally induced gastrin release was independent of cholinergic mechanisms, a potential direct effect of GABA on gastrin release was examined in isolated rabbit antral G cells. In this preparation carbachol (10(-4) M) and neuromedin C (10(-9) M) significantly stimulated gastrin release from 2.6 +/- 0.4 to 4.9 +/- 0.3 and 8.5 +/- 0.9% of the total cellular content, respectively, while GABA (10(-10)-10(-3) M) changed neither basal nor carbachol- and neuromedin C-stimulated gastrin release.
  
  
  CONCLUSIONS
  The present data confirm that exogenous GABA stimulates gastrin release and inhibits somatostatin release from the isolated rat stomach via GABA(A) receptors by activating cholinergic neurotransmission. Furthermore, it was shown for the first time that endogenous GABA contributes to the vagal regulation of gastrin and somatostatin release from the rat stomach. Inhibition of somatostatin secretion by endogenous GABA is mediated by cholinergic mechanisms, whereas stimulation of gastrin release is mediated by pathways unrelated to the cholinergic system and bombesin peptides.
authors.affiliation: Department of Internal Medicine II, Technical University of Munich, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Weigert
authors.forename: W
authors.initials: W
authors.lastname: Schepp
authors.forename: A
authors.initials: A
authors.lastname: Haller
authors.forename: V
authors.initials: V
authors.lastname: Schusdziarra
mesh_terms: D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D001839:Bombesin / Q000378:metabolism*; D018756:GABA Antagonists / Q000494:pharmacology; D005753:Gastric Mucosa / Q000378:metabolism* / Q000502:physiology; D005755:Gastrins / Q000378:metabolism*; D066298:In Vitro Techniques; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D018079:Receptors, GABA / Q000187:drug effects; D013004:Somatostatin / Q000378:metabolism*; D014630:Vagus Nerve / Q000187:drug effects / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology* / Q000502:physiology*
chemical_list: D018756:GABA Antagonists; D005755:Gastrins; D018377:Neurotransmitter Agents; D018079:Receptors, GABA; D013004:Somatostatin; D005680:gamma-Aminobutyric Acid; D001839:Bombesin; D001640:Bicuculline